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A Strategy for the Development of New Antimycotics Acting on the Cell Wall and Cell Membrane of Fungi

https://doi.org/10.37489/0235-2990-2025-70-9-10-62-76

EDN: SXJVHW

Abstract

Background. Invasive mycoses pose a growing health threat, especially for patients with weakened immune systems, whose number is increasing due to advances in oncology, transplantation, and intensive care. The limitations of existing antimycotics are their toxicity, narrow spectrum of action, low bioavailability, and growing resistance of pathogens. The slow pace of development of new antifungal agents compared to antibacterial ones exacerbates the situation, which makes the search for new effective and safe drugs critical. The aim of this review was to summarize and systematize information on current trends in the development of antimycotics, covering both the evolution of approaches to «classical» targets (cell wall, cell membrane) and strategies aimed at overcoming the current limitations of antifungal therapy. Methods. A systematic analysis of scientific literature and clinical research data was carried out using Google Scholar, eLibrary, PubMed, Wally, and ClinicalTrials.gov databases. The main focus was on the publications of the last decade, taking into account the key earlier studies. Results. Over the past 10 years, only 4 new drugs have entered clinical practice. There are 9 molecules in active clinical trials, including Gwt1 inhibitors, dihydroorotate dehydrogenases, and inhaled triazoles. Compounds with new mechanisms of action are of particular interest, for example, mandimycin, which targets phospholipids, inhibitors of inositol-phosphoceramide synthase, which is absent in humans. Conclusion. Despite the challenges associated with the eukaryotic nature of fungi, the development of new antimycotics continues in several promising areas focused on improving the properties of representatives of existing classes, as well as searching for fundamentally new targets.

About the Authors

A. V. Avtonomova
Gause Institute of New Antibiotics
Russian Federation

Anastasia V. Avtonomova — Ph. D. in Biology, Senior Researcher at the Laboratory of Biosynthesis of Biologically Active Substances

Moscow


Competing Interests:

The authors declare that there is no conflict of interest related to the publication of this article. 



O. V. Kisil
Gause Institute of New Antibiotics
Russian Federation

Olga V. Kisil — Ph. D. in Chemistry, Academic Secretary

Moscow


Competing Interests:

The authors declare that there is no conflict of interest related to the publication of this article. 



L. N. Lysenkova
Gause Institute of New Antibiotics
Russian Federation

Lyudmila Nikolaevna Lysenkova — Ph. D. in Biology, Senior Researcher at the Laboratory of Chemical Transformation of Antibiotics

Moscow


Competing Interests:

The authors declare that there is no conflict of interest related to the publication of this article. 



L. M. Krasnopolskaya
Gause Institute of New Antibiotics
Russian Federation

Larissa M. Krasnopolskaya — D. Sc. in Biology, Leading Researcher, Head of the Laboratory of Biosynthesis of Biologically Active Substances

Moscow


Competing Interests:

The authors declare that there is no conflict of interest related to the publication of this article. 



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Avtonomova AV, Kisil OV, Lysenkova LN, Krasnopolskaya LM. A Strategy for the Development of New Antimycotics Acting on the Cell Wall and Cell Membrane of Fungi. Antibiotiki i Khimioterapiya = Antibiotics and Chemotherapy. 2025;70(9-10):62-76. (In Russ.) https://doi.org/10.37489/0235-2990-2025-70-9-10-62-76. EDN: SXJVHW

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